Previous studies on Philadelphia chromosome positive (Ph+) CML and ALL have demonstrated that similar chromosome abnormalities (t(9;22)(q34;qll)) have resulted in (1) juxtaposition of c-abl to the middle portion of the bcr gene resulting in bcr-abl fused mRNA and protein in CML and ALL with a rearranged central region of bcr (Ph+, bcr+ cases) and (2) juxtaposition of c-abl to other unidentified sequences, resulting in novel c-abl mRNA and p190 protein product in Ph+, bcr- ALL cases (without rearrangement of the central region of bcr). To study the structure of the translocated c-abl gene in Ph+ bcr- ALL. we have isolated and sequenced cDNA clones covering the 5' end of the translocated c- abl fused mRNA from an established All cell line. Sequencing of the cDNA clone revealed that the c-abl second exon was fused to the 5' most exon of the bcr gene. This bcr 5' exon cDNA will be used to: isolate 5' __-genomic clones, to walk in the 3' direction of the bcr gene to the ALL breakpoint. and to define an All breakpoint cluster. Probes from the All break region (bcrALL) will be used to determine if changes in the All break region occur in Ph- acute leukemias and during transition from chronic to acute phase of CML. Poly A+ mRNA from All and CML cell lines will be used to develop a modified polymerase chain reaction method to amplify ALL type bcr-abl junctions from an mRNA template. The method will be used to detect residual disease aFter treatment in acute leukemia or emergence of All-type rearrangements, a possible indication of onset of acute phase, in chronic phase CML patients. Additionally, three new bcr-like loci have been described and mapped to chromosome 22 relative to the CML bcr gene. We will isolate and characterize genomic clones for these genes in order to localize and orient these genes relative to chromosome 22-linked genes and breakpoints.